Displacement by tamoxifen of the estradiol-estrogen receptor binding: a functional assay for breast cancer studies.
Displacement curves with estradiol (E2) and Tamoxifen (Tam) of the [3H]E2-ER binding in 49 ER+ mammary neoplasia showed a great heterogeneity suggesting the existence of more than one population of ER+ tumors when the relative binding affinity of both ligands for the ER was considered. The (D50E2/D50Tam) x 100 ratio was called Displacement Index (DI) with values asymmetrically distributed from 0.05 to 2.90. The range from 0.18 to 0.54 was adopted as central interval given by the median +/- SE (median: 0.36; SE: 0.09). DI values below 0.18 (24% of the tumors in our series) were considered as "lower", indicating that higher Tam doses would be necessary to displace the E2-ER binding. The potency of Tam as displacer is dependent not only of its own affinity for the ER, but also of that of E2 for the same receptor. The DI expresses their relative binding "strength". DI values were not correlated with ER and progesterone receptor content nor with the D50 Tam and D50E2 taken separately. Antiestrogen binding sites (AEBS) were determined in the cytosol (AEBSc) and in the microsomal fraction of 10 ER+ tumors from our series. The AEBSc/ER ratio was inversely correlated with the DI, that is, displacement of 3HE2 from the E2-ER complex by Tam would be lower in tumors with higher AEBSc/ER ratio. The DI is another parameter to be considered in the study of the sensitivity of breast neoplasias to antiestrogen treatments.
Levin
E
E
Departamento de Bioquimica, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Tomchinsky
S
S
López
S
S
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism*; D014316:Tritium
D011960:Receptors, Estrogen; D013629:Tamoxifen; D014316:Tritium; D004958:Estradiol